%0 Journal Article
%T Effects of Peptide on NK Cell-Mediated MHC I Recognition
%A Sorcha A. Cassidy
%A Kuldeep S. Cheent
%A Salim I. Khakoo
%J Frontiers in Immunology
%D 2014
%I Frontiers Media
%R 10.3389/fimmu.2014.00133
%X The inhibitory receptors for MHC class I have a central role in controlling natural killer (NK) cell activity. Soon after their discovery, it was found that these receptors have a degree of peptide selectivity. Such peptide selectivity has been demonstrated for all inhibitory killer cell immunoglobulin-like receptor (KIR) tested to date, certain activating KIR, and also members of the C-type lectin-like family of receptors. This selectivity is much broader than the peptide specificity of T cell receptors, with NK cell receptors recognizing peptide motifs, rather than individual peptides. Inhibitory receptors on NK cells can survey the peptide:MHC complexes expressed on the surface of target cells, therefore subsequent transduction of an inhibitory signal depends on the overall peptide content of these MHC class I complexes. Functionally, KIR-expressing NK cells have been shown to be unexpectedly sensitive to changes in the peptide content of MHC class I, as peptide:MHC class I complexes that weakly engage KIR can antagonize the inhibitory signals generated by engagement of stronger KIR-binding peptide:MHC class I complexes. This property provides KIR-expressing NK cells with the potential to recognize changes in the peptide:MHC class I repertoire, which may occur during viral infections and tumorigenesis. By contrast, in the presence of HLA class I leader peptides, virus-derived peptides can induce a synergistic inhibition of CD94:NKG2A-expressing NK cells through recruitment of CD94 in the absence of NKG2A. On the other hand, CD94:NKG2A-positive NK cells can be exquisitely sensitive to changes in the levels of MHC class I. Peptide antagonism and sensitivity to changes in MHC class I levels are properties that distinguish KIR and CD94:NKG2A. The subtle difference in the properties of NK cells expressing these receptors provides a rationale for having complementary inhibitory receptor systems for MHC class I.
%K KIR
%K NKG2A
%K CD94
%K peptides
%K MHC class I
%K natural killer cells
%K antagonism
%K synergy
%U http://www.frontiersin.org/Journal/10.3389/fimmu.2014.00133/abstract